BDNF expression mediates verbal learning and memory in women in a cohort enriched with risk for Alzheimer's disease

Introduction: This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain-derived neurotrophic factor (BDNF) expression.

Methods: In a sample of n = 201 participants (63.81 ± 6.04 years, 66.2% female, 65.7% family history of Alzheimer's disease [AD], 38% apolipoprotein E [APOE] ε4+) from the Wisconsin Registry for Alzheimer's Prevention, VLM was measured using trials 3 through 5 and delayed recall from the Rey Auditory Verbal Learning Test. Plasma BDNF was measured using a Human BDNF Quantikine Immunoassay. Mediation analysis used bootstrapping, and stratified mediation models tested the conditional dependence of APOE ε4 carriage.

Results: BDNF partially mediated the sex-VLM relationship (β = -0.07; 95% confidence interval [CI]: -0.18, -0.01). Female APOE ε4 carriers had higher VLM scores (β = -0.53; p = 0.03), while female non-carriers had both higher BDNF levels (β = -0.68; p < 0.01) and VLM scores (β = -1.06; p < 0.01); BDNF was again a significant mediator (β = -0.18; 95% CI: -0.37, -0.05).

Discussion: This study found that circulating BDNF mediates higher verbal memory scores in females-particularly in APOE ε4 non-carriers.

Highlights: Sex differences in verbal learning and memory (VLM) were mediated by plasma brain-derived neurotrophic factor (BDNF) levels.Women exhibited higher VLM scores and plasma BDNF levels compared to men.The protective effect of BDNF in women was attenuated by apolipoprotein E ε4 carriage.Findings suggest sex-specific mechanisms against verbal memory decline in aging.